An apparent genetic variant of protein 3, the 90,000 molecular weight component which comprises approximately 25 percent of the protein of human erythrocyte membrane, has been identified. The variant polypeptide has a higher molecular weight of approximately 3,000. A random population of 150 individuals indicates that this variant protein occurs in about 6 percent of the population. The major objectives in the next year will be focused upon a determination of the site within the polypeptide structure which is altered in this variant and the amino acid sequence of the altered portion. The biological changes that result from the variant polypeptide will also be investigated. A body of evidence indicates that this protein is involved in facilitated anion transport. Anion and glucose transport by cells with the variant protein will be thoroughly investigated. Phosphorylation of membrane proteins is involved in cell shape changes and protein 3 is phosphorylated by ATP. The effect of the variant protein on cell shape changes and on the interaction of protein 3 with glyceraldehyde phosphate dehydrogenase and the spectrin complex will also be investigated. BIBLIOGRAPHIC REFERENCE: Mueller, T.J. and Morrison, M.: Heterogeneity of the Major Protein in the Human Erythrocyte Membrane. Fed. Proc., 30: 747 (1977).